Neurons associated with a chronic spinal cord injury have the capacity to their axonal process if an appropriate environment, such as a neural tissue transplant, is provided. Experiments employing a double labeling scheme have demonstrated that many of these neurons retain the potential for axonal regeneration for an extended (at least 4 weeks) post injury period. The observation that the regenerative response of axotomized sensory neurons could be enhanced following implantation of a nitrocellulose strip treated with nerve growth factor (NGF) further increases the excitement generated by these transplantation studies. Experiments are proposed to test the hypothesis that exposure to substrate bound trophic factors, in combination with neurotransplantation procedures, can promote the regrowth and guidance of axons and the integration of these processes with the injured spinal cord. Quantitative image analysis, immunocytochemistry, and neuroanatomical tracing techniques will be used to determine if axonal regrowth by chronically injured neurons can be enhanced and guided by substrate bound trophic factors co-grafted with either fetal spinal cord (FSC) tissue or a peripheral nerve (PN) graft (Specific Aim I). Whether the potential for regeneration by chronically injured neurons is restricted to a specific post injury period and whether different types of neurons have comparable regenerative capabilities will be studied in experiments of Aim II. The ability of substrate bound trophic factors to promote the structural and functional integration of regrowing axons with the injured spinal cord will be examined in Aim III by immunocytochemical, tract tracing and electrophysiological techniques. The significance of this study is three fold: 1) it will define populations of chronically injured neurons that retain the capacity for axonal regeneration, 2) it will establish the ability of substrate bound trophic factors to influence the extent and direction of axonal regrowth by injured neurons, and 3) it will indicate whether functional contacts are formed by the structural integration of regenerating axons with surviving regions of the injured spinal cord.
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